Fusion protein comprising three binding domains to 5T4 and CD3

Abstract

The present invention relates to a bispecific binding molecule comprising three binding domains, wherein a first and/or a second binding domain are capable of binding to the extracellular 5T4 antigen and the remaining binding domain(s) is (are) capable of binding to the CD3 receptor complex on T cells. Moreover, the invention relates to a nucleic acid sequence encoding fusion protein, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates to a process for the production of the fusion protein of the invention, a medical use of said fusion protein and a kit comprising said fusion protein.

The invention claimed is: 
     
       1. A heterodimer of fusion proteins comprising two different chains, wherein (i) one chain comprises two VH antibody binding domains, one VL antibody binding domain and one CH1 or CL antibody domain, and (ii) the other chain comprises two VL antibody binding domains, one VH antibody binding domain and one CL or CH1 antibody domain, provided that the fusion protein contains one heterodimer interaction between the CH 1  antibody domain of one chain and the CL antibody domain of the other chain, characterized in that (a) two combined VH/VL binding domains formed within said heterodimer of fusion proteins are capable of binding to the extracellular 5T4 antigen; and (b) the remaining one combined VH/VL binding domain formed within said heterodimer of fusion proteins is capable of binding to the CD3 receptor complex on T cells, wherein one chain has at least 90% identity with SEQ ID NO: 51 and comprises the following CDR sequences:
 SYYMH (SEQ ID NO: 53), 
 RINPNNGVTLYNQKFKD (SEQ ID NO: 54), 
 STMITNYVMDY (SEQ ID NO: 55), 
 SGYTFTRYTMH (SEQ ID NO: 56), 
 YINPSRGYTNYNQKFKD (SEQ ID NO: 57), 
 YYDDHYSL (SEQ ID NO: 58), 
 RASSSVSYMN (SEQ ID NO: 59), 
 DTSKVAS (SEQ ID NO: 60), and 
 QQWSSNPL (SEQ ID NO: 61), 
 
       and the other chain has at least 90% identity with SEQ ID NO: 52 and comprises the following CDR sequences:
 KASQSVSNDVA (SEQ ID NO: 62), 
 YTSSRYA (SEQ ID NO: 63), 
 QQDYNSPPT (SEQ ID NO: 64), 
 SYYMH (SEQ ID NO: 53), 
 RINPNNGVTLYNQKFKD (SEQ ID NO: 54), and STMITNYVMDY (SEQ ID NO: 55). 
 
     
     
       2. A heterodimer of fusion proteins fusion protein according to  claim 1 , wherein one chain comprises at least 95% identity with SEQ ID NO: 51 and the other chain comprises at least 95% identity with SEQ ID NO: 52. 
     
     
       3. A heterodimer of fusion proteins according to  claim 1 , wherein one chain comprises SEQ ID NO: 51 and the other chain comprises SEQ ID NO: 52. 
     
     
       4. A pharmaceutical composition comprising a heterodimer of fusion proteins according to  claim 1 . 
     
     
       5. A kit comprising a heterodimer of fusion proteins as defined in  claim 1 . 
     
     
       6. A nucleic acid sequence encoding a heterodimer of fusion proteins as defined in  claim 1 . 
     
     
       7. A process for the production of a heterodimer of fusion proteins, said process comprising culturing a host cell comprising the nucleic acid of  claim 6  under conditions allowing the expression of the heterodimer of fusion proteins and recovering the produced heterodimer of fusion proteins from the culture.